Evaluating center performance in the competing risks setting: Application to outcomes of wait‐listed end‐stage renal disease patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142886/1/biom12739_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142886/2/biom12739.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142886/3/biom12739-sup-0001-SuppData.pd

Critical Review of Methods for Sampling, Analysis, and Monitoring of Vapor-Phase Toluene Diisocyanate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91959/1/TLVpaper2002.pd

Bhoo Samruddhi : A Compendium of Success Stories, Research Report IDC-2

Across the world, rainfed areas are hotspots of poverty, malnutrition and degradation of natural resources. In India, of 142 m ha of arable lands, 60% is rainfed. Karnataka has the second largest area under rainfed agriculture only after Rajasthan in the country. Farmers’ crop yields in dryland areas are quite low (1.0 -1.5 t ha-1), about two to five times below potential yield. Recent findings from the ‘Comprehensive Assessment of Water for Food and Water for Life’ revealed that the millennium development goal of reducing the number of poor people by half can be met only through efficient use of scarce water resources for agriculture. Food production can be increased substantially in rainfed areas by applying enhanced water use efficiency measures, improving soil health status, and implementing other new technologies in an integrated approach. It is evident that the vast potential of rainfed agriculture can be unlocked by using available scientific technologies including improved cultivars. Recognizing the problem, the Department of Agriculture (DoA), Government of Karnataka (GoK), has adopted science-led initiatives for achieving impact oriented development in the state. In this endeavor, it has sought to bring in international expertise to unlock the potential of rainfed agriculture in the state. Bhoochetana, the farmer-centric initiative taken up by GoK has benefited more than 4.3 million farm households in the state. In addition, the government has initiated a number of innovative measures to improve agricultural production and livelihood of farmers in the state during the last four years. Realizing high impacts in terms of increased agricultural productivity, increased gross value of agriculture production and improved livelihoods, the state government requested ICRISAT to lead a consortium of CGIAR institutions working in India, and to operationalize impact oriented research for development with the aim of improving rural livelihoods. The ICRISAT-led consortium took up this challenge and established a “proof of concept” for translating strategic research knowledge into improving livelihoods through scaling up of the participatory research for development (PR4D) model. A number of meetings and stakeholder consultations were held to identify constraints and problems of all four pilot locations, and the project was begun in 2013-14..

Interactions between zinc oxide nanoparticles and hexabromocyclododecane in simulated waters

The zinc oxide nanoparticles (ZnO-NPs) have been increasingly applied in industries and consumer products, causing release of these nanoparticles in environments. The behaviour of ZnO-NPs in the water systems is complicated due to the presence of different cations, anions, organic substances (e.g. humic acid HA) and other organic pollutants (e.g. commonly used brominated flame retardant, BFR). In particular, the aggregation and alteration of these nanoparticles can be influenced by co-existence contaminants. In this study, the interactions between hexabromocyclododecane (HBCD) and ZnO-NPs were investigated for the physicochemical properties and colloidal stability changes in various simulated waters. This is significant to understand the fate and behaviour of ZnO-NPs at environmental relevant conditions. The surface chemistry and particle size distribution (PSD) of ZnO-NPs with and without the existence of HBCD, HA and electrolytes (NaCl, CaCl2 and MgCl2) after different periods (1 and 3 weeks) were investigated at pH 7.00 ± 0.02. The size of the ZnO-NPs increased from nanometres to micrometres with the addition of numerous concentrations of HBCD, HA, and cations and their mixtures. The zeta potential of ZnO-NPs increased upon addition of HBCD, HA and electrolytes indicating a more stable agglomeration form while less agglomeration was observed in the ZnO-NPs and HA suspension after 3 weeks. Hydrophobic and electrostatic interactions, van der Waals forces, including hydrogen bonding and cation bridging could be potential interactive driving forces. The results indicated agglomeration of ZnO-NPs in the existence of organic substances, salts and contaminants, thus sedimentation and precipitation are promising under salty surface water/sea water

Readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia among young and middle-aged adults: a retrospective observational cohort study

BACKGROUND: Patients aged ≥ 65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among patients aged 18-64 years with patients aged ≥ 65 years. METHODS AND FINDINGS: We used an all-payer administrative dataset from California consisting of all hospitalizations for HF (n=206,141), AMI (n=107,256), and pneumonia (n=199,620) from 2007-2009. The primary outcomes were unplanned 30-day readmission rate, timing of readmission, and readmission diagnoses. Our findings show that the readmission rate among patients aged 18-64 years exceeded the readmission rate in patients aged ≥ 65 years in the HF cohort (23.4% vs. 22.0%, p<0.001), but was lower in the AMI (11.2% vs. 17.5%, p<0.001) and pneumonia (14.4% vs. 17.3%, p<0.001) cohorts. When adjusted for sex, race, comorbidities, and payer status, the 30-day readmission risk in patients aged 18-64 years was similar to patients ≥ 65 years in the HF (HR 0.99; 95%CI 0.97-1.02) and pneumonia (HR 0.97; 95%CI 0.94-1.01) cohorts and was marginally lower in the AMI cohort (HR 0.92; 95%CI 0.87-0.96). For all cohorts, the timing of readmission was similar; readmission risks were highest between days 2 and 5 and declined thereafter across all age groups. Diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions among age groups <65 years; a non-cardiac diagnosis represented 39-44% of readmissions in the HF cohort and 37-45% of readmissions in the AMI cohort, while a non-pulmonary diagnosis represented 61-64% of patients in the pneumonia cohort. CONCLUSION: When adjusted for differences in patient characteristics, young and middle-aged adults have 30-day readmission rates that are similar to elderly patients for HF, AMI, and pneumonia. A generalized risk after hospitalization is present regardless of age.Isuru Ranasinghe, Yongfei Wang, Kumar Dharmarajan, Angela F. Hsieh, Susannah M. Bernheim, Harlan M. Krumhol

Bhoochetana : A Compendium of Success Stories, Research Report IDC-3

The Government of Karnataka has upscaled the learnings from the Sujala-ICRISAT initiative to enhance agricultural productivity in the dryland areas of the state by bridging the yield gap between farmers’ fields and achievable yields with the help of science-based productivity enhancement interventions. The mission project on rainfed agriculture called “Bhoochetana” was launched by the Government of Karnataka during 2009-10 to benefit dryland farmers in 30 districts. The principle of consortium, convergence, capacity building and collective action as proposed by ICRISAT to address the issues of efficiency, economics, equity and environmental protection was adopted. The consortium partners involved in Bhoochetana are three State Agricultural Universities (UAS, Bangalore; Dharwad; and Raichur;), the Watershed Development Department (WDD), the Department of Economics and Statistics (DES), and other line departments of the Government of Karnataka, ICRISAT and the Department of Agriculture which is the nodal agency for the mission project. Farm facilitators and Lead farmers have assumed the role of trainers to train large numbers of farmers on collective action and capacity building. During the second and third year, project activities were expanded to all 30 districts in addition to the six districts of the Sujala watershed program where soil health mapping had already been completed, along with participatory selection of appropriate cultivars of the major crops. In all 30 districts efforts have been made to collect soil samples by adopting a stratified soil sampling method and covering a large number of villages..

The medically managed patient with severe symptomatic aortic stenosis in the TAVR era: Patient characteristics, reasons for medical management, and quality of shared decision making at heart valve treatment centers

Background Little is known about patients with severe symptomatic aortic stenosis (AS) who receive medical management despite evaluation at a heart valve treatment center. Objective We identified patient characteristics associated with medical management, physician-reported reasons for selecting medical management, and patients’ perceptions of their involvement and satisfaction with treatment selection. Methods and results Of 454 patients evaluated for AS at 9 established heart valve treatment centers from December 12, 2013 to August 19, 2014, we included 407 with severe symptomatic AS. Information was collected using medical record review and survey of patients and treating physicians. Of 407 patients, 212 received transcatheter aortic valve replacement (TAVR), 124 received surgical aortic valve replacement (SAVR), and 71 received medical management (no SAVR/TAVR). Thirty-day predicted mortality was higher in patients receiving TAVR (8.7%) or medical management (9.8%) compared with SAVR (3.4%) (P<0.001). Physician-reported reasons for medical management included patient preference (31.0%), medical futility (19.7%), inoperability/anatomic infeasibility (11.3%), and inadequate vascular access (8.5%). Compared with patients receiving AVR, medically managed patients were less likely to report that they received enough information about the pros and cons of treatment options (P = 0.03), that their physicians involved them in treatment decisions (P<0.001), and that final decisions were the right ones (P<0.001). Conclusions Patient preference was the most common physician-reported reason for selecting non-invasive AS management, yet patients not undergoing AVR after valve center evaluation reported being less likely to receive sufficient education about treatment options and more likely to feel uncertain about final treatment decisions. Greater attention to shared decision making may improve the experience of care for this vulnerable group of patients

Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

Epigenetic regulation of the secreted frizzled-related protein family in human glioblastoma multiforme

Glioblastoma multiforme (GBM) are intracranial tumors of the central nervous system and the most lethal among solid tumors. Current therapy is palliative and is limited to surgical resection followed by radiation therapy and temozolomide treatment. Aberrant WNT pathway activation mediates not only cancer cell proliferation but also promotes radiation and chemotherapeutic resistance. WNT antagonists such as the secreted frizzled-related protein (sFRP) family have an ability to sensitize glioma cells to chemotherapeutics, decrease proliferation rate and induce apoptosis. During tumor development, sFRP genes (1–5) are frequently hypermethylated, causing transcriptional silencing. We investigated a possible involvement of methylation-mediated silencing of the sFRP gene family in human GBM using four human glioblastoma cell lines (U87, U138, A172 and LN18). To induce demethylation of the DNA, we inhibited DNA methyltransferases through treatment with 5-azacytidine. Genomic DNA, RNA and total protein were isolated from GBM cells before and after treatment. We utilized bisulfite modification of genomic DNA to examine the methylation status of the respective sFRP promoter regions. Pharmacological demethylation of the GBM cell lines demonstrated a loss of methylation in sFRP promoter regions, as well as an increase in sFRP gene-specific mRNA abundance. Western blot analysis demonstrated an increased protein expression of sFRP-4 and increased levels of phosphorylated-ß-catenin. These data indicate an important role of methylation-induced gene silencing of the sFRP gene family in human GBM

A framework for feature extraction from hospital medical data with applications in risk prediction

Background: Feature engineering is a time consuming component of predictive modeling. We propose a versatile platform to automatically extract features for risk prediction, based on a pre-defined and extensible entity schema. The extraction is independent of disease type or risk prediction task. We contrast auto-extracted features to baselines generated from the Elixhauser comorbidities. Results: Hospital medical records was transformed to event sequences, to which filters were applied to extract feature sets capturing diversity in temporal scales and data types. The features were evaluated on a readmission prediction task, comparing with baseline feature sets generated from the Elixhauser comorbidities. The prediction model was through logistic regression with elastic net regularization. Predictions horizons of 1, 2, 3, 6, 12 months were considered for four diverse diseases: diabetes, COPD, mental disorders and pneumonia, with derivation and validation cohorts defined on non-overlapping data-collection periods. For unplanned readmissions, auto-extracted feature set using socio-demographic information and medical records, outperformed baselines derived from the socio-demographic information and Elixhauser comorbidities, over 20 settings (5 prediction horizons over 4 diseases). In particular over 30-day prediction, the AUCs are: COPD-baseline: 0.60 (95% CI: 0.57, 0.63), auto-extracted: 0.67 (0.64, 0.70); diabetes-baseline: 0.60 (0.58, 0.63), auto-extracted: 0.67 (0.64, 0.69); mental disorders-baseline: 0.57 (0.54, 0.60), auto-extracted: 0.69 (0.64,0.70); pneumonia-baseline: 0.61 (0.59, 0.63), auto-extracted: 0.70 (0.67, 0.72). Conclusions: The advantages of auto-extracted standard features from complex medical records, in a disease and task agnostic manner were demonstrated. Auto-extracted features have good predictive power over multiple time horizons. Such feature sets have potential to form the foundation of complex automated analytic tasks